Optimization of sentinel lymph node biopsy in breast cancer using an operative gamma camera

<p>Abstract</p> <p>Background</p> <p>Sentinel lymph node (SLN) procedure is now a widely accepted method of LN staging in selected invasive breast cancers (unifocal, size ≤ 2 cm, clinically N0, without previous treatment). Complete axillary clearance is no longer needed if the SLN is negative. However, the oncological safety of this procedure remains to be addressed in randomized clinical trials. One main pitfall is the failure to visualize SLN, resulting in incorrect tumor staging, leading to suboptimal treatment or axillary recurrence. Operative gamma cameras have therefore been developed to optimize the SLN visualization and the quality control of surgery.</p> <p>Case presentation</p> <p>A 44-year-old female patient with a 14-mm infiltrative ductal carcinoma underwent the SLN procedure. An operative gamma camera was used during and after the surgery. The conventional lymphoscintigraphy showed only one SLN, which was also detected by the operative gamma camera, then removed and measured (9.6 kBq). It was analyzed by frozen sections, showing no cancer cells. During this analysis, the exploration of the axillary area with the operative gamma camera enabled the identification of a second SLN with low activity (0.5 kBq) that conventional lymphoscintigraphy, surgical probe and blue staining had failed to visualize. Histological examination revealed a macrometastasis. Axillary clearance was then performed, followed by a postoperative image proving that no SLN remained. Therefore, the use of the operative gamma camera prevented an under-estimation of staging which would have resulted in a suboptimal treatment for this patient.</p> <p>Conclusion</p> <p>This case report illustrates that an efficient operative gamma camera may be able to decrease the risk of false negative rate of the SLN procedure, and could be an additional tool to control the quality of the surgery.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov Identifier: NCT00357487</p

Altered Negative Unconscious Processing in Major Depressive Disorder: An Exploratory Neuropsychological Study

Major depressive disorder (MDD) has been characterized by abnormalities in emotional processing. However, what remains unclear is whether MDD also shows deficits in the unconscious processing of either positive or negative emotions. We conducted a psychological study in healthy and MDD subjects to investigate unconscious emotion processing and its valence-specific alterations in MDD patients.We combined a well established paradigm for unconscious visual processing, the continuous flash suppression, with positive and negative emotional valences to detect the attentional preference evoked by the invisible emotional facial expressions.Healthy subjects showed an attentional bias for negative emotions in the unconscious condition while this valence bias remained absent in MDD patients. In contrast, this attentional bias diminished in the conscious condition for both healthy subjects and MDD.Our findings demonstrate for the first time valence-specific deficits specifically in the unconscious processing of emotions in MDD; this may have major implications for subsequent neurobiological investigations as well as for clinical diagnosis and therapy

Facial expressions depicting compassionate and critical emotions: the development and validation of a new emotional face stimulus set

Attachment with altruistic others requires the ability to appropriately process affiliative and kind facial cues. Yet there is no stimulus set available to investigate such processes. Here, we developed a stimulus set depicting compassionate and critical facial expressions, and validated its effectiveness using well-established visual-probe methodology. In Study 1, 62 participants rated photographs of actors displaying compassionate/kind and critical faces on strength of emotion type. This produced a new stimulus set based on N = 31 actors, whose facial expressions were reliably distinguished as compassionate, critical and neutral. In Study 2, 70 participants completed a visual-probe task measuring attentional orientation to critical and compassionate/kind faces. This revealed that participants lower in self-criticism demonstrated enhanced attention to compassionate/kind faces whereas those higher in self-criticism showed no bias. To sum, the new stimulus set produced interpretable findings using visual-probe methodology and is the first to include higher order, complex positive affect displays

Sensory theories of developmental dyslexia: three challenges for research.

Recent years have seen the publication of a range of new theories suggesting that the basis of dyslexia might be sensory dysfunction. In this Opinion article, the evidence for and against several prominent sensory theories of dyslexia is closely scrutinized. Contrary to the causal claims being made, my analysis suggests that many proposed sensory deficits might result from the effects of reduced reading experience on the dyslexic brain. I therefore suggest that longitudinal studies of sensory processing, beginning in infancy, are required to successfully identify the neural basis of developmental dyslexia. Such studies could have a powerful impact on remediation.This is the accepted manuscript. The final version is available from NPG at http://www.nature.com/nrn/journal/v16/n1/abs/nrn3836.html

The development of spontaneous facial responses to others’ emotions in infancy. An EMG study

Viewing facial expressions often evokes facial responses in the observer. These spontaneous facial reactions (SFRs) are believed to play an important role for social interactions. However, their developmental trajectory and the underlying neurocognitive mechanisms are still little understood. In the current study, 4- and 7-month old infants were presented with facial expressions of happiness, anger, and fear. Electromyography (EMG) was used to measure activation in muscles relevant for forming these expressions: zygomaticus major (smiling), corrugator supercilii (frowning), and frontalis (forehead raising). The results indicated no selective activation of the facial muscles for the expressions in 4-month-old infants. For 7-month-old infants, evidence for selective facial reactions was found especially for happy faces (leading to increased zygomaticus major activation) and fearful faces (leading to increased frontalis activation), while angry faces did not show a clear differential response. This suggests that emotional SFRs may be the result of complex neurocognitive mechanisms which lead to partial mimicry but are also likely to be influenced by evaluative processes. Such mechanisms seem to undergo important developments at least until the second half of the first year of life

A Non-Specific Effect Associated with Conditional Transgene Expression Based on Cre-loxP Strategy in Mice

Transgenes flanked by loxP sites have been widely used to generate transgenic mice where the transgene expression can be controlled spatially and temporally by Cre recombinase. Data from this approach has led to important conclusions in cancer, neurodevelopment and neurodegeneration. Using this approach to conditionally express micro RNAs (miRNAs) in mice, we found that Cre-mediated recombination in neural progenitor cells caused microcephaly in five of our ten independent transgenic lines. This effect was not associated with the types or the quantity of miRNAs being expressed, nor was it associated with specific target knockdown. Rather, it was correlated with the presence of multiple tandem transgene copies and inverted (head-to-head or tail-to-tail) transgene repeats. The presence of these inverted repeats caused a high level of cell death in the ventricular zone of the embryonic brain, where Cre was expressed. Therefore, results from this Cre-loxP approach to generate inducible transgenic alleles must be interpreted with caution and conclusions drawn in previous reports may need reexamination

Recognition Profile of Emotions in Natural and Virtual Faces

BACKGROUND: Computer-generated virtual faces become increasingly realistic including the simulation of emotional expressions. These faces can be used as well-controlled, realistic and dynamic stimuli in emotion research. However, the validity of virtual facial expressions in comparison to natural emotion displays still needs to be shown for the different emotions and different age groups. METHODOLOGY/PRINCIPAL FINDINGS: Thirty-two healthy volunteers between the age of 20 and 60 rated pictures of natural human faces and faces of virtual characters (avatars) with respect to the expressed emotions: happiness, sadness, anger, fear, disgust, and neutral. Results indicate that virtual emotions were recognized comparable to natural ones. Recognition differences in virtual and natural faces depended on specific emotions: whereas disgust was difficult to convey with the current avatar technology, virtual sadness and fear achieved better recognition results than natural faces. Furthermore, emotion recognition rates decreased for virtual but not natural faces in participants over the age of 40. This specific age effect suggests that media exposure has an influence on emotion recognition. CONCLUSIONS/SIGNIFICANCE: Virtual and natural facial displays of emotion may be equally effective. Improved technology (e.g. better modelling of the naso-labial area) may lead to even better results as compared to trained actors. Due to the ease with which virtual human faces can be animated and manipulated, validated artificial emotional expressions will be of major relevance in future research and therapeutic applications

Piccolo genotype modulates neural correlates of emotion processing but not executive functioning

Major depressive disorder (MDD) is characterized by affective symptoms and cognitive impairments, which have been associated with changes in limbic and prefrontal activity as well as with monoaminergic neurotransmission. A genome-wide association study implicated the polymorphism rs2522833 in the piccolo (PCLO) gene—involved in monoaminergic neurotransmission—as a risk factor for MDD. However, the role of the PCLO risk allele in emotion processing and executive function or its effect on their neural substrate has never been studied. We used functional magnetic resonance imaging (fMRI) to investigate PCLO risk allele carriers vs noncarriers during an emotional face processing task and a visuospatial planning task in 159 current MDD patients and healthy controls. In PCLO risk allele carriers, we found increased activity in the left amygdala during processing of angry and sad faces compared with noncarriers, independent of psychopathological status. During processing of fearful faces, the PCLO risk allele was associated with increased amygdala activation in MDD patients only. During the visuospatial planning task, we found no genotype effect on performance or on BOLD signal in our predefined areas as a function of increasing task load. The PCLO risk allele was found to be specifically associated with altered emotion processing, but not with executive dysfunction. Moreover, the PCLO risk allele appears to modulate amygdala function during fearful facial processing in MDD and may constitute a possible link between genotype and susceptibility for depression via altered processing of fearful stimuli. The current results may therefore aid in better understanding underlying neurobiological mechanisms in MDD

Genome-wide association scan identifies new variants associated with a cognitive predictor of dyslexia

Developmental dyslexia (DD) is one of the most prevalent learning disorders, with high impact on school and psychosocial development and high comorbidity with conditions like attention-deficit hyperactivity disorder (ADHD), depression, and anxiety. DD is characterized by deficits in different cognitive skills, including word reading, spelling, rapid naming, and phonology. To investigate the genetic basis of DD, we conducted a genome-wide association study (GWAS) of these skills within one of the largest studies available, including nine cohorts of reading-impaired and typically developing children of European ancestry (N = 2562-3468). We observed a genome-wide significant effect (p <1 x 10(-8)) on rapid automatized naming of letters (RANlet) for variants on 18q12.2, within MIR924HG (micro-RNA 924 host gene; rs17663182 p = 4.73 x 10(-9)), and a suggestive association on 8q12.3 within NKAIN3 (encoding a cation transporter; rs16928927, p = 2.25 x 10(-8)). rs17663182 (18q12.2) also showed genome-wide significant multivariate associations with RAN measures (p = 1.15 x 10(-8)) and with all the cognitive traits tested (p = 3.07 x 10(-8)), suggesting (relational) pleiotropic effects of this variant. A polygenic risk score (PRS) analysis revealed significant genetic overlaps of some of the DD-related traits with educational attainment (EDUyears) and ADHD. Reading and spelling abilities were positively associated with EDUyears (p similar to [10(-5)-10(-7)]) and negatively associated with ADHD PRS (p similar to [10(-8)-10(-17)]). This corroborates a long-standing hypothesis on the partly shared genetic etiology of DD and ADHD, at the genome-wide level. Our findings suggest new candidate DD susceptibility genes and provide new insights into the genetics of dyslexia and its comorbities.Peer reviewe